Neuropathy I NeuroNetwork
photo of Dr. Melissa Elafros checking a patient for signs of diabetic neuropathy

Untangling the complexities of peripheral nerve health.

The Problem

Neuropathy occurs when peripheral nerves become damaged or dysfunctional. This nerve damage can manifest in various symptoms, including numbness, tingling, burning pain, and muscle weakness, leading to chronic pain, mobility issues, increased risk of injuries due to reduced sensation, and significantly reduced quality of life. Neuropathy is estimated to affect over 20 million people in the United States, with diabetes being a leading cause. According to the Global Burden of Disease Study 2021, diabetic neuropathy is one of the top 10 neurological conditions that cause ill health and disability worldwide, underscoring the critical need for effective management and prevention strategies.  

  • Approximately half of all individuals with diabetes will develop neuropathy at some point during the disease.  

  • There is no cure for diabetic neuropathy, and control of blood glucose levels does not reverse neuronal loss.  

nerve axons shown in red, myelin shown in green and inflammatory markers in blue
Nerve axons (red), myelin (green), inflammatory markers (blue)

Our work continues to demonstrate that metabolic factors beyond diabetes, such as obesity, damage peripheral nerves and influence the development of neuropathy and other neurological disorders. Therefore, one of our main focuses is to understand how obesity and diabetes damage the peripheral nervous system, leading to neuropathy. Our ultimate goal is to translate these findings into effective treatment and prevention strategies.  

  • Clinical research suggests that certain diets, such as the ketogenic diet, may protect or improve nerve health. 

  • Studies show that exercise may help prevent or treat neuropathy. 
Our neuropathy program launches
The overarching goal? Determine how diabetes damages nerves to develop novel therapies for diabetic neuropathy.
Feldman lab in 2007 Feldman lab in 2007
Advances in screening
Develop the Michigan Neuropathy Screening Instrument (MNSI), a questionnaire and physical foot examination used by researchers worldwide to diagnose neuropathy.
questions from the Michigan Neuropathy Screening Instrument questions from the Michigan Neuropathy Screening Instrument
Oxidative stress
Link oxidative stress, an imbalance of toxic free radicals and antioxidants, to neuropathy.
A macrophage engulfing oxidized lipids and damaged cells as part of the bodys immune response to oxidative stress A macrophage engulfing oxidized lipids and damaged cells as part of the bodys immune response to oxidative stress
Preclinical models
Publish our first report characterizing mouse models of diabetic neuropathy.
Michigan Blue Pantonne Michigan Blue Pantonne
Major funding support
Receive a 15-year multi-investigator grant from NIH to assess mechanisms underlying diabetic complications affecting the nerve. (image shows nerve fibers (green) in an animal model)
nerve fibers shown in green in an image taking from an animal model nerve fibers shown in green in an image taking from an animal model
Triglycerides
Using nerves from patients with neuropathy, identify the link between triglycerides, a type of fat in the blood, and the progression of nerve loss.
triglycerides in the blood triglycerides in the blood
Novel technology
Discover genes and related signaling pathways that contribute to nerve degeneration in diabetes using advanced bioinformatics techniques.
Gene co-citation network clustered by fast-greedy community structuring algorithm Gene co-citation network clustered by fast-greedy community structuring algorithm
Bioenergetics
Evaluate how bioenergetics (the way cells process sugars and fats to make energy) contribute to nerve damage in diabetes. (photo shows nerve fibers (green) that have been damaged from diabetes)
More discoveries related to fats and neuropathy
Confirm factors other than glucose, such as lipids (fats), contribute to neuropathy in patients with type 2 diabetes.
Neurotransmitters
Show people with diabetes and neuropathy have an imbalance of brain neurotransmitters, molecules that transmit brain signals.
nerve fiber shown in green that was damaged from diabetes nerve fiber shown in green that was damaged from diabetes
Working together
Form the International Diabetic Neuropathy Consortium with colleagues from Denmark and the United Kingdom to better understand and support neuropathy prevention and treatment.
people who were part of the International Diabetic Neuropathy Consortium people who were part of the International Diabetic Neuropathy Consortium
Managing neuropathy
Inform the American Diabetes Association of guidelines for the management of diabetic neuropathy.
American Diabetes Association logo in red and black American Diabetes Association logo in red and black
Obesity as a risk factor
Determine obesity, particularly fat concentrated around the waist, damages peripheral nerves and drives peripheral neuropathy independent of diabetes.
Fat vs. sugar
Confirm altered lipids are more detrimental than elevated glucose for nerve health.
doctor measuring an obese man's waist doctor measuring an obese man's waist
What we eat matters
Demonstrate eating a diet with unsaturated fats prevents and improves neuropathy.
More mechanistic insights
Identify inflammation as a driver of neuropathy.
Epigenetics
Demonstrate genes and pathways relevant to diabetic neuropathy are under epigenetic control, a mechanism that regulates gene function without changing DNA sequences.
food photo food photo
The problem with fat
Report changes in nerve triglycerides leads to neuropathy.
More insight into obesity and neuropathy
Show where fat collects in the body is more important than overall obesity in determining the risk of developing neuropathy.
doctor measuring an obese man's waist doctor measuring an obese man's waist
Fat vs. fat
Demonstrate diets rich in saturated fats (red meat) cause poor nerve function, while diets rich in unsaturated fats (olive oil or avocado) do not.
Clinical Insights
Discover different lipid species in the plasma of people with obesity and type 2 diabetes compared to lean controls.
Flint Neuropathy Study
Launch Flint Neuropathy Study to determine the connection between prediabetes, diabetes, obesity, and nerve health in a patient cohort from Flint, Michigan. (photo is from the Flint Neuropathy Study)
photo of Dr. Melissa Elafros checking a patient for signs of diabetic neuropathy photo of Dr. Melissa Elafros checking a patient for signs of diabetic neuropathy
Research support
Five-year project is funded by NIH to examine effects of diet and exercise on peripheral nerve function in mouse models of obesity, prediabetes, and diabetes.
Stem cells
Harness the power of stem cells and mouse models to understand how nerve and supporting cells (Schwann cells) impact nerve health and metabolism.
a group of Schwann cells a group of Schwann cells
NEUROPATHY INITIATIVES
Lifestyle Interventions

Growing evidence indicates that changes in diet and exercise can prevent diabetic neuropathy and improve brain health.

Schwann cells

Research suggests that metabolic dysregulation, such as obesity or type 2 diabetes (T2D), disrupts Schwann cell function, leading to nerve damage and peripheral neuropathy.

Extracellular vesicles

Small, membrane-bound particles released by cells that play a crucial role in cell-to-cell communication.

Pain

Studying pain in neurological conditions to develop effective diagnostic and treatment options.

Flint Neuropathy Study

Understanding the extent of undiagnosed diabetes and neuropathy among primary care patients in Flint, Michigan.